Improving health-related quality of life (HRQOL) is a key treatment goal for children with Juvenile Idiopathic Arthritis (JIA), but there is a gap in our knowledge of how medical and non-medical variables determine HRQOL in the context of ongoing treatment. Our long-term goal is to improve HRQOL for children with JIA. The specific objective of the study is to determine the pathways by which medical variables (biological, physiological, clinical, physical function) and non-medical variables (individual, family, environmental characteristics) predict HRQOL in children being actively treated for JIA. Our central hypothesis is that, for children with JIA undergoing treatment, HRQOL is determined, in part, by biological, physiological, clinical, and functional variables and that individual, family, and environmental variables have both direct and indirect effects on HRQOL. We will recruit new JIA patients aged 5 to 16 years (n = 224) and perform a one-year prospective longitudinal cohort study to accomplish the following specific aims: #1) Determine the pathways by which medical variables (biological, physiological, clinical, physical function) predict HRQOL in children being treated for JIA; #2) Determine the extent to which non-medical characteristics of the child, family, and environment explain additional variance, beyond medical factors, in HRQOL in children being treated for JIA. The rationale for the proposed research is that successful completion of this project will lead to a thorough understanding of the drivers of between-patient differences in HRQOL outcomes and to identification of additional therapeutic targets, thus enabling clinicians to maximize HRQOL for children with JIA and to maximize the effect of JIA treatments on HRQOL. The proposed study is innovative in that it represents a novel approach to understanding the determinants of HRQOL and the potential effects of clinical interventions on HRQOL. It is anticipated that the study will yield the following expected outcomes'. First, we will have a better understanding of determinants of HRQOL in children with JIA within the context of treatment. Second, we will have identified specific, modifiable factors that could be targeted to improve HRQOL and to improve the effect of JIA treatments on HRQOL. Third, we will have developed a rich database to reveal trends in these relationships over time and identify further areas for study. Relevance to public health: Improving HRQOL is a fundamental goal of the US health care system, yet too little is known about the ways in which changes in medical variables as a result of treatment interact with non-medical variables to produce changes in HRQOL. Our objective and specific aims are consistent with NIAMS's long-range plan to improve HRQOL for Americans affected by diseases of bones, muscles, joints, and skin. This research represents a step towards ensuring optimal HRQOL for children with JIA and for other chronically ill children.